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Complement activation by cross-linked truncated and chimeric full-length beta-amyloid.
- Source :
-
Neuroreport [Neuroreport] 1997 Nov 10; Vol. 8 (16), pp. 3457-62. - Publication Year :
- 1997
-
Abstract
- The activation of complement by beta-amyloid (A beta) has been implicated in the local inflammatory response in Alzheimer's disease. To assess the structural parameters required for this activation, beta-sheet-containing fibrils of A beta1-28 were induced by low pH and then chemically cross-linked to constrain the beta-sheet conformation. Chimeric A beta peptides with a substituted C-terminal sequence derived from two different transmembrane proteins were also assessed for the ability to form fibrils rich in beta-sheet structure and to activate complement. Both the cross-linked A beta1-28 and the chimeric A beta peptides were strong activators of the classical complement pathway. These results suggest that the C-terminal residues (29-42) of A beta facilitate fibril assembly required for complement activation but do not contain the interaction sites required for complement activation, further supporting the hypothesis that C1q binds to the N-terminal hydrophilic domain of A beta, and that a fibrillar beta-sheet-rich conformation is required for effective binding and activation of C1.
- Subjects :
- Amino Acid Sequence
Amyloid beta-Peptides chemistry
Animals
Binding Sites
Complement C1q drug effects
Complement C1q metabolism
Cross-Linking Reagents
Ethyldimethylaminopropyl Carbodiimide
Guinea Pigs
Humans
Molecular Sequence Data
Peptide Fragments chemistry
Protein Conformation
Protein Structure, Secondary
Recombinant Fusion Proteins chemistry
Recombinant Fusion Proteins pharmacology
Sequence Deletion
Amyloid beta-Peptides pharmacology
Complement Activation drug effects
Peptide Fragments pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0959-4965
- Volume :
- 8
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- Neuroreport
- Publication Type :
- Academic Journal
- Accession number :
- 9427307
- Full Text :
- https://doi.org/10.1097/00001756-199711100-00009